Amity Institute of Neuropsychology & Neurosciences, Amity University, Noida, 201303, India.
Doping research chair, Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
Mol Neurobiol. 2021 May;58(5):1875-1893. doi: 10.1007/s12035-020-02266-w. Epub 2021 Jan 6.
Although COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30-60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a systems biology-based network approach and observed a remarkable resemblance. Our results showed 123 brain-related disorders associated with COVID-19 and form a high-density disease-disease network. The brain-disease-gene network revealed five highly clustered modules demonstrating a greater complexity of COVID-19 infection. Moreover, we have identified 35 hub proteins of the network which were largely involved in the protein catabolic process, cell cycle, RNA metabolic process, and nuclear transport. Perturbing these hub proteins by drug repurposing will improve the clinical conditions in comorbidity. In the near future, we assumed that in COVID-19 patients, many other neurological manifestations will likely surface. Thus, understanding the infection mechanisms of SARS-CoV-2 and associated comorbidity is a high priority to contain its short- and long-term effects on human health. Our network-based analysis strengthens the understanding of the molecular basis of the neurological manifestations observed in COVID-19 and also suggests drug for repurposing.
虽然 COVID-19 主要引起呼吸道并发症,但它也可导致各种肺外表现,导致更高的死亡率,这些合并症对医疗保健系统构成挑战。有报道称,30-60%的 COVID-19 患者有神经系统症状。为了了解 COVID-19 患者神经合并症的分子基础,我们通过基于系统生物学的网络方法研究了 COVID-19 与各种脑部疾病的遗传关联,并观察到了显著的相似性。我们的研究结果表明,与 COVID-19 相关的有 123 种与大脑相关的疾病,并形成了一个高密度的疾病-疾病网络。大脑疾病-基因网络揭示了五个高度聚集的模块,表明 COVID-19 感染的复杂性更大。此外,我们还鉴定了网络中的 35 个枢纽蛋白,它们主要参与蛋白质分解代谢过程、细胞周期、RNA 代谢过程和核转运。通过药物再利用来干扰这些枢纽蛋白将改善合并症的临床状况。在不久的将来,我们假设在 COVID-19 患者中,可能会出现许多其他神经系统表现。因此,了解 SARS-CoV-2 的感染机制及其相关合并症是遏制其对人类健康的短期和长期影响的当务之急。我们的基于网络的分析加强了对 COVID-19 中观察到的神经表现的分子基础的理解,并为药物再利用提供了建议。